Jason A BaileyDepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana, United States of AmericaPLoS ONE 6:e21954. 2011

Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway

Debomoy K LahiriDepartment of Psychiatry, Indiana University School of Medicine Indianapolis, IN USA Laboratory of Medical and Molecular Genetics, Indiana University School of Medicine Indianapolis, IN, USA Institute of Psychiatric Research, Indiana University School of Medicine Indianapolis, IN, USAFront Cell Neurosci 7:94. 2013

..These data demonstrate a pathway by which p25/cdk5 increases the amyloidogenic processing of APP through STAT3-mediated transcriptional control of BACE1 that could have implications for AD pathogenesis...

..Therefore, our findings suggest that IVIG treatment may represent an important therapeutic agent for clinical trials designed to prevent and delay the onset of neurodegeneration as well as AD pathology...

Autism as early neurodevelopmental disorder: evidence for an sAPPα-mediated anabolic pathway

Debomoy K LahiriDepartment of Psychiatry, Indiana University School of Medicine Indianapolis, IN USA Laboratory of Medical and Molecular Genetics, Indiana University School of Medicine Indianapolis, IN, USA Institute of Psychiatric Research, Indiana University School of Medicine Indianapolis, IN, USAFront Cell Neurosci 7:94. 2013

..The possibility of a single metabolic-cognitive disorder opens up the possibility of unified preventative treatments that reduce monetary and social costs of disease. LEARn suggests specific, testable pathways within the large theory...

..Characterization of the activity of a regulatory polymorphism of the APP gene points towards understanding mechanisms that likely underlie the majority of AD cases and may contribute to promoter-based drug design...

Characterization of the APP proximal promoter and 5'-untranslated regions: identification of cell type-specific domains and implications in APP gene expression and Alzheimer's disease

..Therefore, the -46/54 region appears to be essential for basal expression of the APP gene, the 54/100 and 100/144 regions may have tissue-specific activity, and the "amyloid" CAGA box plays a role in APP gene regulation...

Role of the APP promoter in Alzheimer's disease: cell type-specific expression of the beta-amyloid precursor protein

..Finally, we examine different neurobiological mechanisms that provide the basis of new targets for AD drug development...

Apolipoprotein E as a target for developing new therapeutics for Alzheimer's disease based on studies from protein, RNA, and regulatory region of the gene

Debomoy K LahiriDepartment of Psychiatry and of Medical and Molecular Genetics, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USAJ Mol Neurosci 23:225-33. 2004

..The interaction of different transcription factors with the regulatory region of the ApoE gene is important to understand the neuroinflammatory process seen in AD...

Melatonin affects the metabolism of the beta-amyloid precursor protein in different cell types

..Taken together, these data suggest that melatonin probably affects the secretion of sAPP in the conditioned medium by interfering with its full maturation, and melatonin also affects the presysnaptic terminal marker...

Apolipoprotein gene and its interaction with the environmentally driven risk factors: molecular, genetic and epidemiological studies of Alzheimer's disease

..The divergent actions of these two structurally related drugs on the amyloid pathway indicate that the mechanisms underpinning the cholinergic and the amyloid-lowering properties for this class of drugs are independent of each other...

..Our results suggest that mAPOE can also be expressed in neuronal cells in addition to the astrocytic cells. Characterization of mAPOE promoter is important for the AD drug development discovery and APOE transgenic mice studies...

The role of the carboxyl-terminal fragments of amyloid precursor protein in Alzheimer's disease

..We speculate that any structural alteration(s) due to a specific mutation in these regulatory regions can potentially alter the transcriptional machinery, and that can perhaps affect the level of beta-amyloid protein involved in AD...

Effect of a memory-enhancing drug, AIT-082, on the level of synaptophysin

Balmiki RayDepartment of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USANeurosci Lett 470:1-5. 2010

..Such a novel property of memantine warrants further study to define its therapeutic utility...

A novel effect of rivastigmine on pre-synaptic proteins and neuronal viability in a neurodegeneration model of fetal rat primary cortical cultures and its implication in Alzheimer's disease

Jason A BaileyLaboratory of Molecular Neurogenetics, Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USAJ Neurochem 112:843-53. 2010

..Phenserine was most efficient to block translation under conditions of intracellular iron chelation with desferrioxamine suggesting that this anticholinesterase operated through an iron (metal)-dependent pathway at the APP 5'-UTR site...

Functional characterization of three single-nucleotide polymorphisms present in the human APOE promoter sequence: Differential effects in neuronal cells and on DNA-protein interactions

..This favors an increased alpha-secretase pathway in autism (anabolic), opposite to what is seen in Alzheimer disease. Additionally, a complex relationship between age, acetylcholinesterase, and plasma neuronal markers was found...

Characterization of the human beta-secretase 2 (BACE2) 5'-flanking region: identification of a 268-bp region as the basal BACE2 promoter

..These lead drugs are readily testable to measure APP holoprotein expression in a cell based secondary assay, and by use of an APP transgenic mouse model to test potential beneficial effects of lead drug treatments on amyloid burden...

A single copy of carbonic anhydrase 2 restores wild-type circadian period to carbonic anhydrase II-deficient mice

..The phenotype of the new lines showed that the long circadian period characteristic of the CA-II-deficient mice arises when functional CA-II is absent, not when DBA/2J alleles are present on proximal chromosome three...

Neuroinflammation in Alzheimer's disease: different molecular targets and potential therapeutic agents including curcumin

..Thus, based on the reported positive preliminary results reviewed herein, further research is required to develop the full potential of AGE and/or SAC into an effective preventative strategy for AD...

..Samples collected have been shown to produce usable DNA after shipment through conventional mail. The DNA produced by rapid elution of these swabs in chaotropic buffers is, however, of limited quality and low purity...

Lead (Pb) exposure and its effect on APP proteolysis and Abeta aggregation

..These data suggested that environmental influences occurring during brain development predetermined the expression and regulation of APP later in life, potentially altering the course of amyloidogenesis...

Gene structure and organization of the human beta-secretase (BACE) promoter

Kumar SambamurtiMedical University of South Carolina, Charleston, South Carolina, USAFASEB J 18:1034-6. 2004

..Such a study will allow us to further examine the possible role of changes in the promoter of BACE in AD pathogenesis...

Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine

..These results suggest that within the brain, levels of total sAPP, sAPPgamma and, accordingly, Abeta are subject to cholinergic manipulation, offering therapeutic potential at the level of AbetaPP processing to decrease Abetadeposition...

Identification of novel small molecule inhibitors of amyloid precursor protein synthesis as a route to lower Alzheimer's disease amyloid-beta peptide

..Translation of APP and A beta actions to mice was demonstrated with one agent. They thus represent interesting lead molecules for assessment in animal models, to define their tolerance and utility as potential AD therapeutics...

Aluminum and copper in drinking water enhance inflammatory or oxidative events specifically in the brain

..Collectively, these data suggest that GLP-1 can modify APP processing and protect against oxidative injury, two actions that suggest a novel therapeutic target for intervention in Alzheimer's disease...

..The development of specific BuChE inhibitors and further experience with the dual enzyme inhibitor rivastigmine will improve understanding of the aetiology of AD and should lead to a wider variety of potent treatment options...